Influence of immunohistochemistry on the final diagnosis of breast biopsies.

AIMS: Because of the introduction of mammography screening programmes in Europe, the number of breast biopsies performed is increasing. We investigated the influence of immunohistochemistry (IHC) on the final diagnosis of breast biopsies by comparing the primary diagnoses (based on the results of haematoxylin and eosin staining only) with the final diagnoses (based on the additional information provided by IHC). METHODS AND RESULTS: We analysed the breast biopsies which were performed at the University of Halle-Wittenberg between 2006 and 2010 and for which the pathologist requested IHC for making the final diagnosis. According to the B-categorization scheme, the primary diagnosis changed in 37 of a total of 429 biopsies (8.6%). In 18 of these biopsies (48.6%) the category changed from B1-B2 to B3-B5 or vice versa, which would imply a different work-up. Only 77% of the primary diagnoses of breast cancer in situ were confirmed. CONCLUSION: IHC has a considerable influence on the final diagnosis of breast biopsies in several situations, including those in which the biopsied women are at risk of inadequate therapeutic intervention. The influence is particularly notable among those biopsies for which IHC is performed in order to assess the suspicion of breast cancer in situ.

Mammographic density and inter-observer variability of pathologic evaluation of core biopsies among women with mammographic abnormalities.

BACKGROUND: As high percentage of mammographic densities complicates the assessment of imaging findings, mammographic density may influence the histopathological evaluation of core-biopsies of the breast. We measured the influence of mammographic density on the inter-observer variability of histopathological findings of breast biopsies. METHODS: Histological slides of 695 women who underwent core biopsies of the breast at University of Halle between 2006 and 2008 were evaluated in a blinded fashion by two pathologists using the five levels of the B-categorization scheme (B1-B5). To quantify mammographic density, we used a computer-based threshold method (Madena). We calculated observed and chance-corrected agreements (weighted kappa) and 95% confidence intervals (95% CI) according to four categories of mammographic density (<10%, 10<25%, 25<50%, ≥50%). RESULTS: The weighted kappa decreased monotonically from 89.6% (95% CI: 85.8%, 93.3%) among women with less than 10% of mammographic density to 80.4% (95% CI: 69.9%, 90.9%) for women with more than 50% of mammographic density, respectively. Results of a kappa regression analysis showed that agreement of pathologists on clinically relevant categories (B1-B2 versus B3-B5) decreased with mammographic density. CONCLUSIONS: Mammographic density is a relevant modifier of the agreement between pathologists who assess breast biopsies using the B-categorization scheme. The influence of mammographic density on the inter-observer variability can be explained to some extent by varying prevalences of histological entities across B categories that have typically different inter-observer agreement. Women with high mammographic density are at higher risk of inter-observer variability compared to women with low mammographic density and should possibly undergo a second pathology review.

Factors influencing the agreement on histopathological assessments of breast biopsies among pathologists.

AIMS: It has been recommended that the histopathology results of core biopsies of the breast are categorized according to the B-categorization scheme. We measured the interobserver variability of the B-categorization of core biopsies of the breast. METHODS AND RESULTS: Core biopsies were taken among 765 women at the University of Halle between 2006 and 2008. All histological slides were reviewed in a blinded fashion by two experienced breast pathologists. We calculated observed and chance-corrected agreements (kappa) and 95% confidence intervals (CI). The prevalence of B3-B5 biopsies was 41.6%. The observed and weighted kappa agreement of the five-level B-categorization scheme was 0.87 (95% CI: 0.84 -0.89) and 0.89 (95% CI: 0.89-0.91), respectively. The most frequent disagreement was between B2 and B3 (47 of 103 disagreements, 45.6%). Overall, 49.5% of all disagreements were clinically relevant disagreements that would imply different therapeutic strategies. Agreement was modified by referral group, Breast Imaging Reporting and Data System (BIRADS) level, radiological breast density, imaging guidance and application of immunohistological staining. CONCLUSIONS: Interobserver agreement of the B-categorization scheme was high and was modified by referral status, level of radiological suspicion of breast cancer, breast density, imaging guidance of core biopsies and requirement of additional immunohistological staining.

Primary breast sarcoma: prevalence, clinical signs, and radiological features.

BACKGROUND: Primary breast sarcoma is very rare. Most reports regarding sarcoma of the breast are clinical observations or pathological series and provide either no or inconstant radiological information. Radiological publications consist predominantly of isolated case reports or small series. PURPOSE: To determine the prevalence, clinical signs, and radiological features of primary breast sarcoma. MATERIAL AND METHODS: This is a retrospective review of 21 patients with breast sarcoma. All patients were female and their median age was 66 years (range 27-86). In all patients the diagnosis was confirmed histopathologically. RESULTS: The prevalence of breast sarcoma was 0.1% of all identified cases with breast malignancies. Clinically, all patients presented with solitary painless breast lumps. There was no uni- or bilateral axillary lymphadenopathy. On mammography (n = 19), two mammographic patterns could be identified: breast masses (68%), and architectural distortion (32%). On ultrasound (n = 8), most lesions were homogeneously hypoechoic, lobular or oval in shape with microlobulated or indistinct margins. On magnetic resonance imaging (n = 3), marked inhomogeneous contrast enhancement was seen in all investigated cases. CONCLUSION: The imaging findings of primary breast sarcoma are not pathognomonic. However, they should be taken into consideration in the differential diagnosis of breast lesions.

Metastases to the breast from non-mammary malignancies: primary tumors, prevalence, clinical signs, and radiological features.

RATIONALE AND OBJECTIVES: Most secondary intramammary tumors occur as metastatic involvement from the contralateral breast. Breast metastases (BM) from nonmammary malignancies are very rare. The aims of this study were to estimate retrospectively the prevalence of BM from nonmammary malignancies and to describe their radiologic appearance. MATERIALS AND METHODS: BM were identified in 51 patients, including 43 women and eight men with a median age of 61 years (range, 24-84 years). Computed tomography of the thoracic region identified 108 lesions in 38 patients. Mammography was available for 37 patients (54 lesions). Ultrasound evaluation was performed in 43 patients (71 lesions). In 24 patients (93 lesions), magnetic resonance imaging of the breast was done. Images were reviewed in consensus by two radiologists according to the Breast Imaging Reporting and Data System lexicon. RESULTS: The prevalence of BM in several tumors ranged from 0.12% to 4.92%. On computed tomography, most metastases were round or oval in shape with marked or moderate enhancement. On mammography, solitary or multiple round or oval masses with circumscribed margins were the most common pattern of BM. Ten percent showed microcalcifications. On ultrasound, most BM were hypoechoic, oval or round in shape, with microlobulated or circumscribed margins, and posterior acoustic enhancement. Doppler imaging showed hypervascularity in 39% of BM. On magnetic resonance imaging, most lesions demonstrated marked homogenous contrast enhancement. Type 1 kinetic curve was seen in 18%, type 2 in 52%, and type 3 in 30%. CONCLUSIONS: The radiologic features reported in this study should be taken into consideration in the differential diagnosis of breast lesions.

[18F]Fluorodeoxyglucose positron emission tomography for detection of bone marrow involvement in children and adolescents with Hodgkin's lymphoma.

PURPOSE: Currently, a routine bone marrow biopsy (BMB) is performed to detect bone marrow (BM) involvement in pediatric Hodgkin's lymphoma (HL) stage greater than IIA. [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) is increasingly used for the initial staging of HL. The value of using FDG-PET to detect BM involvement has not been sufficiently defined. We compared the results of BMBs and FDG-PET for the diagnosis of BM involvement in a large pediatric group with HL. PATIENTS AND METHODS: The initial staging of 175 pediatric patients with newly diagnosed classical HL stage greater than IIA was determined by using BMB, FDG-PET, chest computed tomography (CT), and magnetic resonance imaging (MRI) or CT of the neck, abdomen, and pelvis. Staging images were prospectively evaluated by a central review board. Skeletal regions that were suggestive of BM involvement by either method were re-evaluated by using different imaging modalities. In suspicious cases, bone scintigraphy was performed. If follow-up FDG-PET scans were available, the remission of skeletal lesions during treatment was evaluated. RESULTS: BMB results were positive in seven of 175 patients and were identified by FDG-PET. FDG-PET scans showed BM involvement in 45 patients. In addition, the lesions of 32 of these 45 patients had a typical multifocal pattern. In 38 of 39 follow-up positron emission tomography scans, most of the skeletal lesions disappeared after chemotherapy. There was no patient with skeletal findings suggestive of BM involvement by MRI or CT with a negative FDG-PET. CONCLUSION: FDG-PET is a sensitive and specific method for the detection of BM involvement in pediatric HL. The sensitivity of a BMB appears compromised by the focal pattern of BM involvement. Thus, FDG-PET may safely be substituted for a BMB in routine staging procedures.

Procarbazine-free OEPA-COPDAC chemotherapy in boys and standard OPPA-COPP in girls have comparable effectiveness in pediatric Hodgkin's lymphoma: the GPOH-HD-2002 study.

PURPOSE: Vincristine, etoposide, prednisone, and doxorubicin (OEPA)-cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) is derived from standard vincristine, procarbazine, prednisone, and doxorubicin (OPPA)-cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) chemotherapy by replacing procarbazine with etoposide and dacarbazine for a potentially less gonadotoxic regimen for boys with Hodgkin's lymphoma (HL). PATIENTS AND METHODS: Five hundred seventy-three pediatric patients with classical HL were enrolled onto the German Society of Pediatric Oncology and Hematology-Hodgkin's Disease (GPOH-HD) -2002 study between November 2002 and December 2005. Boys received two courses of OEPA and girls received two courses of OPPA for induction. Treatment group (TG) -2 (intermediate stages) and TG-3 (advanced stages) patients received further two or four cycles COPP (girls) or COPDAC (boys), respectively. After chemotherapy all patients received involved-field irradiation with 19.8 Gy, except for patients with early-stage disease (TG-1) in complete remission. RESULTS: Five hundred seventy-three patients (287 males and 286 females) were less than 18 years old and fulfilled all inclusion criteria; 195 patients (34.0%) were allocated to TG-1, 139 (24.3%) were allocated to TG-2, and 239 (41.7%) were allocated to TG-3. Toxicity of OEPA-COPDAC was tolerable overall. Hematotoxicity was more pronounced with OEPA than OPPA, whereas it was less pronounced with COPDAC compared with COPP. The median observation time was 58.6 months. Overall survival and event-free survival (EFS) rates (+/- SE) at 5 years were 97.4% +/- 0.7% and 89.0% +/- 1.4%, respectively. In TG-1, overall EFS was 92.0% +/- 2.0%. EFS of patients without irradiation (93.2% +/- 3.3%) was similar to that of irradiated patients (91.7% +/- 2.5%), confirming results of the previous GPOH-HD-95 study. In TG-2+3, EFS did not significantly differ between boys and girls (90.2% +/- 2.3 v 84.7% +/- 2.7, respectively; P = .12). CONCLUSION: In TG-2+3, results in boys and girls are superimposable. OPPA-COPP and OEPA-COPDAC seem to be exchangeable regimens in intermediate- and advanced-stage classical HL in pediatric patients.